(19f) Quantitative Correlation of the Effect of Process Conditions On the Capping Tendencies of Tablet Formulations

Tablet compaction presses and compaction emulator were used to rank order capping tendencies of a diverse sample set which includes excipients, binary, tertiary blends and final compression blends of commercial products. The compression forces of 5 kN, 10 kN, 15 kN, 20 kN, and 25 kN were studied for oval and round tooling shapes, while 4 kN, 6 kN, 8 kN, 10 kN, and 14 kN were chosen for the beveled edge due to the force restrictions for this tooling. Compaction speeds of 25 rpm (24.8 ms dwell time), 40 rpm (15.5 ms dwell time), and 80 rpm (7.9 ms dwell time) were chosen as representative ranges for bench-to-pilotscale processing. Five replicate tablets were compressed at each of the factor levels to ensure repeatability. Tablets were tested by nondestructive ultrasonic method to obtain effective elastic (E) and shear (G) moduli in the axial and radial directions. The anisotropic properties of tablet formulations are represented by a dimensionless ratio (EG). The ultrasonic measurements revealed that effective elastic and shear modulus values vary with different testing orientations which indicated elastic and shear moduli anisotropy in tablets. It was found that as the EG ratio decreases; the compressed powder exhibited an increasing level of anisotropic nature, which led to a higher tendency for capping. Acceptance criteria of the EG ratio have been proposed based on manufacturing performance. It was shown that altering process conditions such as tooling shape, compression force and press speed significantly affect the capping tendency of tablet formulations. A systematic approach has been applied to develop predictive tools to assess capping tendencies of formulations. These tools have been shown to correlate well with actual capping performance of a diverse sample set. The developed tools are fast, material sparing and have potential to flag the risk of capping issues and provide insight into the performance of common materials during formulation and process development. Application of these tools may help reduce development time, API usage and facilitate development of a robust product.